Idiopathic lower genitourinary tract syndromes in men cause major morbidity and expenditure of health care resources. For example, half of all adult men suffer from "prostatitis" at some time, but the etiology is uncertain for over 90% of affected men. Therapy is empirical and often ineffective because we have limited understanding of the causes. The broad, long-term objective of this proposal is to determine the causes, consequences and optimal therapy for these conditions. Our hypothesis is that genitourinary tract infection causes common idiopathic syndromes, particularly nonbacterial prostatitis, prostatodynia and chronic urethritis. This project has three specific aims. 1) We will determine the role of previously suspected urogenital pathogens (e.g., Chlamydia trachomatis, Trichomonas vaginalis, genital mycoplasmas and viruses) using newly available detection methods. 2) We will investigate the potential role of previously unsuspected microorganisms for which we have promising new detection methods. 3) We will study the relationships among genitourinary infection, inflammation in prostatic secretions, sonographic appearance of the prostate and prostate histopathology. Clinical evaluation will include a standardized history and physical examination, symptom score, urological investigations and lower tract localization studies. Subjects will then have transrectal ultrasound and systematic biopsies of the prostate. Complementary experimental studies will determine the prevalence of infection using optimal culture methods plus highly sensitive polymerase chain reaction techniques. The polymerase chain reaction studies will use specific molecular probes as well as broad-spectrum probes to detect previously unsuspected pathogens. Understanding the etiology of common lower tract syndromes will improve urological evaluation and treatment of millions of men annually in the U.S.